Major: Neuroscience & Child Learning and Development
Research Department: Neuroscience
Graduation Date: December 2020
Abstract: The Neuromuscular Junction (NMJ) is a chemical synapse between a peripheral nervous system branch and a muscle modulated by the neurotransmitter Acetylcholine (ACh). We do not know much about the exact mechanisms and processes behind postnatal synapse development, but we do know that the process is highly regulated by synapse activity. An activity dependent transcription factor, Myocyte enhancing factor (Mef2), has been implicated in governing development, differentiation, and maintenance of various cell types, including neurons and muscle cells. Thus, we hypothesized that Mef2 is required for proper postnatal NMJ development, maturation, and maintenance. For this study, we knocked out the genes Mef2a, 2c, and 2d at P0 by postnatal injection of Cre in triple transgenic Mef2afcfdf mice. At P21, we dissected and imaged the controls and the experimental mice. We observed a significantly greater density of Acetylcholine receptor (AChR) clusters and synapses in the Cre-injected mice. We also observed a greater incidence of axonal oversprouting and drastically smaller AChR cluster areas in the experimental mice. We concluded that Mef2 genes likely suppress the expression of AChRs. Therefore, Mef2 deletion results in reduced suppression and more clusters appear all over the cells and tissues. We also see that Mef2 appears to play a role in targeting presynaptic nerve terminals to clusters. Based on our observations, we hypothesize that Mef2 is involved in cluster stabilization. When deleted, clusters are unstable and fragment. In the future, we can use RNA sequencing to identify the specific genes and proteins affected when Mef2 is deleted, then isolate and delete those individual components to have a better understanding of the details of postnatal NMJ development.
What Does Research Mean To You? The opportunity to contribute to research is my chance to leave my mark on the world around me. The advancement of science is a global effort. Any discovery today, no matter how small, is built upon past research and will continue to be built upon in the future. Every generation of scientists is contributing to advancements in essentially everything in the world from medicine to politics to philosophy. Research is the foundation of innovation and invention. Involvement in research to any extent has been humbling and an excellent learning experience.
Tell Us About Your Journey I began my research career in Dr. Mandy Maguire’s Developmental Neurolinguistics Lab in the summer after my freshman year. Dr. Maguire’s lab uses EEG and various behavioral assessments to learn about how the brain changes as children learn language. I fell in love with the ability to see what we learned in class manifested in real life. I spent two years in Dr. Maguire’s lab learning the ins and outs of computational neuroscience research and contributing to many different lab projects. Yet, when I joined Dr. Weichun Lin’s developmental neurobiology lab, it felt like starting from ground zero. Working in a wet lab was a completely different experience despite both labs focusing on developmental neuroscience. I spent the weeks prior to the Green Fellowship reading paper after paper, trying to familiarize myself with the interests and methods of the lab, but most of what I read went directly over my head. I was familiar with the basic biology and neuroscience behind the research; however, my project was based mostly on genetics, which I had no experience with. There was a steep learning curve; I failed most of my first experiments and dissections, and I made countless mistakes. Nevertheless, my PI, lab members, and the program staff were very encouraging and supportive. Luckily, one of the first projects I undertook yielded promising results. I spent over 50 hours in the lab a week working on the project, but the figures I used for my poster were not finalized until about a week before my presentation. I really enjoyed my experience as a Green Fellow, as it took me behind the scenes of medicine. I witnessed and experienced the process of contributing to the advancement of science: the foundation of every aspect of medicine we have today. Having gone through the tedious tasks of developing a novel research question, implementing the procedure, making adjustments based on observations, and finally, analyzing and presenting the results, I gained a much deeper appreciation and passion for the scientific method.
How Did the Pandemic Affect Me? Going in to the spring 2020 semester, I had some research experience in a computational neuroscience lab. I thoroughly enjoyed that experience to the extent that I began considering pursuing an MD/PhD rather than just the MD I had been planning for so many years. I knew, however, that working in biomedical research would be a completely different experience: different environment, different intensity. I saw the Green Fellowship as an excellent opportunity to gain some exposure to the medical research setting. It was difficult adjusting at first; I was completely lost at the beginning, but my learning grew exponentially. It was really interesting to see things we learned in class applied in the real world. Despite the unexpected interruption due to the pandemic, the hands-on experience taught me much more than a classroom ever could, and I learned information that will stick for the remainder of my academic career. My lab and the program was still very supportive as we transitioned to remote work, and with their support, I was able to make the best of a difficult situation and produce a poster. But what I think was most valuable is what I learned about myself. While I enjoyed going to UTSW every day and working in the lab, I realized that I am better suited for a more clinically-based career, working directly with patients. Especially following Dr. Andrew Zinn’s presentation about the MD/PhD MSTP program, I realized that a career as an MD is best for me. That being said, this experience also showed me that I would still like to remain involved in research throughout the remainder of my career to some extent, as being involved in research fascinated me and made me feel like I was contributing to the betterment of science. But my primary passion remains in clinical practice. I am beyond thankful for this experience and I gained more out of it than I could have ever imagined.
Where am I now? I graduated in December 2020 with my B.S. in Neuroscience and Child Learning and Development. Next year, I will be attending medical school at UT Southwestern.
Advice for Future Green Fellows
Get ready to learn and be tested. Even though there are no formal classes, I learned so much from working hands-on in the lab. To be even remotely successful you need to know the exact processes and scientific mechanisms behind the experiments you are running. That being said, don’t be afraid to make mistakes; everyone may have high expectations of you but you are still expected to mess up! I learned more from the mistakes I made than from the things I did right. Ask questions, no matter how many times someone has explained something to you, don’t be afraid to ask again. Also know that it will not be an easy semester. You will have to persevere through long days and busy weeks. In the end you will look back with a strong sense of accomplishment, proud of how much you learned, how hard you worked, and how you contributed to the advancement of science.